The opioid crisis has influenced practice changes to mitigate risks to patients receiving opioids. It is essential that nurses understand contemporary guidelines to provide safe patient care for patients receiving opioids.This study was designed to assess general knowledge of opioids among nurses in nonprescribing patient care roles.A survey was developed, validated, and deployed to 564 nurses in a large hospital system.Nurses had strong knowledge of basic pharmacology, the conjunctive use of nonopioids for pain relief, and differences in analgesia for chronic versus acute pain. Opportunity for education included risk factors for opioid-related adverse events, medication combinations, differences in opioid tolerant and opioid-naïve patients, and recognition and management of overdose.Results of this study can be used to guide continuing education and academic curricula to ensure nurses are equipped with the key knowledge to provide safe quality clinical care and patient education.